The present invention relates to novel filaments formed from a polymer matrix and from thermoluminescent particles, especially for use as thermoluminescent dosimeters.
It also relates to a method for measuring, by thermoluminescence, the beta radiation doses delivered by an emitter to a target organ of a mammal.
The use of thermoluminescent dosimeters has already been described in internal radiotherapy in patent FR-B-1 470 914.
This patent describes especially polytetrafluoroethylene (PTFE) filaments about 1 mm in diameter, these being filled to about 8% with lithium fluoride microcrystals obtained by extrusion and able to be used in vivo.
Lithium fluoride forms part of the thermoluminescent mineral compounds called xe2x80x9cphosphorsxe2x80x9d, among which mention may also be made of calcium fluoride CaF2 or calcium sulfate CaSO4, to which special activators may possibly be added.
Implantable Dy:CaSO4 mini-dosimeters (B. W. Wessels et al., The Journal of Medicine, Vol. 27, No. 8, August 1986, pp. 1308-1314) have in particular been manufactured by cutting disks of Teflon and CaSO4 with a microtome.
The small dimensions (0.5xc3x970.2xc3x970.4 mm) of these osimeters make it possible to detect large dose gradients during the therapeutic use of beta-emitting radioelements.
Many subsequent studies have been carried out using these Dy:CaSO4 mini-thermoluminescent dosimeters (mini-TLDs). Thus, S-E Strand et al., (Acta Oncologica, Vol. 32, No. 718, pp. 787-791, 1993) have demonstrated the phenomenon of Dy:CaSO4 crystals dissolving in aqueous phase. This leads to a loss of signal in vivo (by 60% for immersion for 9 days at pH 6) making the luminescence measurements at the very least inaccurate. These authors propose covering the dosimeter with a thin layer of Teflon or with other suitable materials.
A. J. Demidecki et al., Med. Phys. 20:1079:1087, 1993 concluded that there was a great difficulty in using Dy:CaSO4 mini-TLDs unless correction factors were applied.
Many subsequent studies have been carried out using these Dy:CaSO4 mini-thermoluminescent dosimeters (mini-TLDs). Thus, S-E Strand et al., (Acta Oncologica, Vol. 32, No. 718, pp. 787-791, 1993) have demonstrated the phenomenon of Dy:CaSO4 crystals dissolving in aqueous phase. This leads to a loss of signal in vivo (by 60% for immersion for 9 days at pH 6) making the luminescence measurements at the very least inaccurate. These authors propose covering the dosimeter with a thin layer of Teflon or with other suitable materials.
A. J. Demidecki et al., Med. Phys. 20:1079:1087, 1993 concluded that there was a great difficulty in using Dy:CaSO4 mini-TLDs unless correction factors were applied.
However, mini-dosimeters have been used in vivo by M. H. Griffith et al., J. Nucl. Med. 1988, 29:1795-1809.
Nevertheless, it is desirable to provide novel mini-thermoluminescent dosimeters which do not have the abovementioned disadvantages, especially in the case of in vivo use.
Unexpectedly, the applicants have shown that improving the adhesion properties between the polymer material and the thermoluminescent particles helps to overcome the drawbacks described above.
It is an object of the present invention to provide novel filaments which can be used in particular to make mini-thermoluminescent dosimeters which:
exhibit excellent mechanical strength and excellent elasticity within the context of in vivo use;
provide effective protection of the TL crystals from an aqueous medium;
show a lack of exchange between content and container (dissolution, chemical reaction);
exhibit satisfactory biocompatibility with tissue;
allow the absorbed radiation dose from a few mGy to a few tens of Gy to be determined with improved accuracy;
have an advantageous manufacturing cost.
One or more of the objects of the invention are achieved by the solution that the patent application provides.
The invention therefore relates to a filament comprising thermoluminescent particles uniformly distributed in a polymer matrix, characterized in that the polymer matrix coating said thermoluminescent particles is a hydrophobic thermoplastic polymer having sufficient adhesion to the thermoluminescent particles to ensure cohesion of the filament and being such that a thermoluminescent response (signal) from the filament corresponding approximately to the absorbed radiation dose is obtained, after the filament has been brought into contact with a physiological medium.
The polymer is therefore such that, after the filament has been immersed in an irradiation physiological medium, the thermoluminescent response (signal) corresponds approximately to the absorbed radiation dose.
The term xe2x80x9cpolymerxe2x80x9d is understood to mean within the context of the present description a homopolymer, a copolymer, a blend of homopolymers or a blend of copolymers.
The term xe2x80x9csufficient adhesionxe2x80x9d is understood to mean that the polymer has a high surface energy, however not exceeding the surface energy of a hydrophilic polymer. PTFE, for example, known for its nonstick properties, has a very low surface energy (its surface energy is 21 mJ/m2 at 20xc2x0 C.). The surface energy of the polymer allowing the invention to be implemented advantageously lies between 25 and 50 mJ/m2 at 20xc2x0 C. and advantageously between 27 and 46 mJ/m2. The expression xe2x80x9ccorresponding approximatelyxe2x80x9d is understood to mean that the response must be at least of the order of 90% with respect to the absorbed dose. That is to say, the response is not affected by prolonged residence of the filament in the physiological medium. In other words, the filament behaves equivalently in air and when it is immersed in a physiological medium. There is practically no loss of response due to immersion in a physiological medium.
The expression xe2x80x9cgood cohesionxe2x80x9d is understood to mean that the filament has a high mechanical strength and retains its physical integrity in a physiological medium.
The thermoluminescent particles are formed from crystals which, after irradiation, have the property of releasing the absorbed energy in the form of light when they are subjected to a sufficiently high temperature. There is storage of the ionization phenomena. The amount of light emitted is then, within certain limits, a linear function of the dose absorbed by the crystal. They can therefore be used as dosimeters. All luminescent particles in powder form may be suitable.
There are a large number of thermoluminescent particles known to those skilled in the art.
Among thermoluminescent particles, mention may especially be made of crystals based on lithium fluoride (LiF), calcium fluoride (CaF2), these possibly being doped with magnesium, copper or phosphorus.
Among polymers which are suitable within the context of the present invention, it is preferred to use those which can be processed using well-known extrusion processes. These polymers must therefore have a melting point below the critical temperature of the thermoluminescent particles so as not to degrade the dosimetric characteristics of the TL material. However, it should be noted that some thermoluminescent materials have a sufficiently high critical temperature for this proviso to be unnecessary (the critical xe2x80x9ctemperaturexe2x80x9d is the limit above which the thermoluminescent material loses its properties of releasing the stored energy).
Among thermoplastic polymers meeting this requirement, mention may be made of nonhalogenated polyolefins, especially polyethylenes, polypropylenes or polyisobutylenes. Among polyethylenes, mention may be made of low-density polyethylenes (LDPEs) or high-density polyethylenes (HDPEs). Polypropylenes have a better mechanical strength than polyethylenes and have a higher melting point.
Among the other extrudable polymers, mention may be made of (co)polymers resulting from the polymerization of vinyl chloride (PVC), acrylic and methacrylic ester polymers, such as polymethyl methacrylate (PMMA), or other equivalent polymers, polystyrenes, polyethylene terephthalates, polyamides and ethylene-vinyl acetate copolymers.
Of course, other polymers able to be processed by extrusion are also suitable.
Preferably, the filaments are obtained by extrusion, that is to say the mixture of thermoluminescent particles in powder form and of polymers in granule or powder form is introduced into the hopper of an extruder, homogenized in a suitable temperature gradient in a barrel provided with an extrusion screw, before being passed through a die of defined diameter.
To obtain good-quality filaments, it will often be required to add, in a known manner, lubricants to the mixture of granules and particles.
The subject of the invention is more particularly micrometric filaments, that is to say filaments whose diameter is less than 1 mm, preferably between 100 and 800 micrometers. In practice in this case, simple extrusion of a mixture of particles and granules without any preparation is not very easy. In order to improve the extrusion, for example for a die 400 micrometers in diameter, it is advantageous to use thermoluminescent particles whose particle size is small. Of course, the particle size depends on the nature of these particles. In general, it is preferred to use particles whose size is less than 90 micrometers, thereby making extrusion more uniform. In addition, the surface finish of the filaments is improved by the use of an internal lubricant (for example, a polyethylene wax or polypropylene wax) and an external lubricant (as antistatic agent) in order to prevent the formation of aggregates.
Preferably, the thermoluminescent particles are present in a proportion of between 10 and 50% by weight with respect to the weight of the filament. Advantageously, the proportion is greater than 25% by weight.
This is because it has been noted that the greater the proportion of particles the smaller the coefficient of variation of the measurements (standard deviation with respect to the mean over ten measurements). Consequently, a high proportion of particles makes it possible to combine the two advantages relating to sensitivity and repeatability of the measurements within the same batch.
The irradiation doses may vary over a very wide range, from a few mGy to 20 Gy, it being possible, of course, for this range of values to vary depending on the nature of the thermoluminescent particles.
After irradiation, reading is carried out in a suitable reader known to those skilled in the art. The heating is carried out by conduction and an optical detection system is used to collect the signal emitted by the thermoluminescent material during heating. This reading is destructive if the polymer matrix has a melting point below the heating temperature, that is to say the dosimeter is a xe2x80x9csingle usexe2x80x9d dosimeter.
Care must be taken, as an additional criterion in respect of the choice of polymer, to ensure that, during reading, the melting of the polymer does not disturb the recorded signal and does not damage the TL reader.
According to another variant, the filament includes an external layer or sheath formed from a hydrophobic thermoplastic polymer alone (without any TL powder), the melting point of which is below the critical temperature of the thermoluminescent particles, and the core is a filament as described above. Preferably, the polymer of the external layer is identical to the polymer matrix. The thickness of the external layer is such that the diameter of the core filament plus the external layer is less than 800 xcexcm.
It will be advantageous to coextrude the external layer in the presence of an external lubricant (polyethylene wax or polypropylene wax, for example). The coextrusion is carried out using the techniques known in the art.
The filaments according to the invention are particularly noteworthy in that they have a very homogeneous distribution of the thermoluminescent particles and in that they provide excellent protection of said thermoluminescent particles against an external medium.
It should in particular be noted that these filaments can be stored in air, or exhibit no degradation in an aqueous medium at variable pH.
It is for this reason that these filaments are advantageously used in vivo so as to determine the dose received by a mammal""s target organ to be treated.
This is why the invention relates to a filament as described above for measuring in vivo, by thermoluminescence, the beta or gamma radiation doses delivered by an emitter in a target organ of a mammal.
The invention also relates to a method for measuring, by thermoluminescence, the beta radiation doses delivered by an emitter in a target organ of a mammal, characterized in that a group of filaments according to the invention is introduced at the desired location, it being possible for part of the length of said filaments to remain outside the irradiated zone, and in that, after irradiation, the filaments are removed and the thermoluminescence determined.
The invention will now be illustrated by the following examples: